Site-specific manipulation of the genome is a desirable goal for many applications in medicine, biotechnology, and biological research. In recent years much effort has been made to develop site-specific nucleases for gene targeting in mitotic and post-mitotic cells in vitro and in vivo. However, these targeted nucleases are often toxic to cells and their off target activity may be immunogenic and genotoxic. What is needed in the art are methods for editing the genome of a cell without the use of exogenously provided nucleases. The present invention addresses these issues.